DNA Methylation Inhibitors

A set of novel DNA methylation inhibitors that reduce DNA methylation by small molecule agents.

The Need

Substantial evidence indicates that DNA methylation-mediated silencing of tumor suppressor genes is a mechanism for the pathogenesis of cancer and many other diseases. Thus, small-molecule agents that target DNA methylation are considered a therapeutically relevant strategy for cancer treatment. The major competitor in the market is a demethylating agent named 5-aza-2’-deoxyctidine, also known as decitabine or 5-aza. However, side-effects of decitabine include cell toxicity, bone marrow suppression, neutropenia, thrombocytopenia, and short half-life.

The Technology

Researchers at The Ohio State University researchers, led by Dr. Ching-Shih Chen, discovered novel structures for DNA methylation inhibitors derived from procainamide, including lead agent IM25. Procainamide and its derivatives safely and effectively inhibit DNA (cytosine-5)-methyltransferase 1 (DNMT1) through a reduction of affinity with its two substrates. Demethylation causes growth arrest and reactivation of tumor suppressor genes in cells, which lead to decreased tumor size and improve prognosis in cancer patients. This invention was funded by the National Science Council (Taiwan) and the National Institutes of Health.

Commercial Applications

  • Biological cancer treatment
  • Therapeutics
  • Pharmaceutical


  • IM25 displays high potency in producing GSTp1 DNA demethylation in cancerous cells
  • Exhibits lower cytotoxicity in MCF7 cells relative to procainamide and other current commercial hypomethylating drugs
  • Long half-life allows effective delivery to tumor sites

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